The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology
Abstract
The progressive degenerative process associated with sporadic Parkinson's disease (sPD) is characterized by formation of alpha-synuclein-containing inclusion bodies in a few types of projection neurons in both the enteric and central nervous systems (ENS and CNS). In the brain, the process apparently begins in the brainstem (dorsal motor nucleus of the vagal nerve) and advances through susceptible regions of the basal mid-and forebrain until it reaches the cerebral cortex. Anatomically, all of the vulnerable brain regions are closely interconnected. Whether the pathological process begins in the brain or elsewhere in the nervous system, however, is still unknown. We therefore used immunocytochemisty to investigate the gastric myenteric and submucosal plexuses in 150 microm cryosections and 8 microm paraffin sections from five autopsy individuals, whose brains were also staged for Parkinson-associated synucleinopathy. alpha-synuclein immunoreactive inclusions were found in neurons of the submucosal Meissner plexus, whose axons project into the gastric mucosa and terminate in direct proximity to fundic glands. These elements could provide the first link in an uninterrupted series of susceptible neurons that extend from the enteric to the central nervous system. The existence of such an unbroken neuronal chain lends support to the hypothesis that a putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“During the first stages of PD, neurons of the ENS and the olfactory bulbs (OB) were found to contain aggregated and phosphorylated alpha-synuclein (Braak et al., 2006;Shannon et al., 2012b).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Braak et al., 2006
In the citing paper
“Several clinical studies revealed that PD patients expressed alphasynuclein accumulation in the ENS (Braak et al., 2006;Forsyth et al., 2011;Gelpi et al., 2014;Gold et al., 2013;Sánchez-Ferro et al., 2015;Shannon et al., 2012a).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Braak et al., 2006
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Self-citationStaging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Self-citationSpillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689
Self-citationBraak, H., R�b, U., Gai, W. P., & Del Tredici, K. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0808-2 · Cited by 1,683
Self-citationGastrointestinal dysfunction in Parkinson's disease
Pfeiffer, R. F. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00307-7 · Cited by 933
Where Does Parkinson Disease Pathology Begin in the Brain?
Del Tredici, K., Rüb, U., de Vos, R. A. I., Bohl, J. R. E., & Braak, H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.5.413 · Cited by 773
Self-citationParkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses
Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E., & Ikuta, F. (1988) · Acta Neuropathologica · doi:10.1007/bf00687767 · Cited by 528
Anatomy and physiology of the enteric nervous system
Costa, M., Brookes, S., & Hennig, G. (2000) · Gut · doi:10.1136/gut.47.suppl_4.iv15 · Cited by 364
Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough
Lang, A. E., & Obeso, J. A. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00740-9 · Cited by 348
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–122 of 122
Gastrointestinal Dysfunction in Parkinson’s Disease
Pfeiffer, R. F. (2018) · Current Treatment Options in Neurology · doi:10.1007/s11940-018-0539-9 · Cited by 94
Antibiotic Exposure and Risk of Parkinson's Disease in Finland: A Nationwide Case‐Control Study
Mertsalmi, T. H., Pekkonen, E., & Scheperjans, F. (2020) · Movement Disorders · doi:10.1002/mds.27924 · Cited by 88
Pellegrini, C., Fornai, M., Colucci, R., Tirotta, E., Blandini, F., Levandis, G., Cerri, S., Segnani, C., Ippolito, C., Bernardini, N., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0608-5 · Cited by 91
Oral and Gut Dysbiosis Leads to Functional Alterations in Parkinson’s Disease
Jo, S., Kang, W., Hwang, Y. S., Lee, S. H., Park, K. W., Kim, M. S., Lee, H., Yoon, H. J., Park, Y. K., Chalita, M., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00351-6 · Cited by 85
O’Donovan, S. M., Crowley, E. K., Brown, J. R. ‐., O’Sullivan, O., O’Leary, O. F., Timmons, S., Nolan, Y. M., Clarke, D. J., Hyland, N. P., Joyce, S. A., et al. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.13726 · Cited by 86
The gut-brain axis and Parkinson disease: Clinical and pathogenetic relevance
Menozzi, E., Macnaughtan, J., & Schapira, A. H. V. (2021) · Annals of Medicine · doi:10.1080/07853890.2021.1890330 · Cited by 81
Parkinson's Disease Is Associated with Impaired Gut–Blood Barrier for Short‐Chain Fatty Acids
Yang, X., Ai, P., He, X., Mo, C., Zhang, Y., Xu, S., Lai, Y., Qian, Y., & Xiao, Q. (2022) · Movement Disorders · doi:10.1002/mds.29063 · Cited by 82
Linking Smoking, Coffee, Urate, and Parkinson’s Disease – A Role for Gut Microbiota?
Scheperjans, F., Pekkonen, E., Kaakkola, S., & Auvinen, P. (2015) · Journal of Parkinson’s Disease · doi:10.3233/jpd-150557 · Cited by 83
Gastrointestinal autonomic dysfunction in patients with Parkinson’s disease
Kim, J.-S., & Sung, H.-Y. (2015) · Journal of Movement Disorders · doi:10.14802/jmd.15008 · Cited by 76
Wang, H., Chen, G., Ahn, E. H., Xia, Y., Kang, S. S., Liu, X., Liu, C., Han, M.-H., Chen, S., & Ye, K. (2023) · npj Parkinson's Disease · doi:10.1038/s41531-022-00430-8 · Cited by 71
Chen, T.-J., Feng, Y., Liu, T., Wu, T.-T., Chen, Y.-J., Li, X., Li, Q., & Wu, Y.-C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.549037 · Cited by 69
Hyposialorrhea as an early manifestation of Parkinson disease
Cersósimo, M. G., Tumilasci, O. R., Raina, G. B., Benarroch, E. E., Cardoso, E. M., Micheli, F., & Pazo, J. H. (2009) · Autonomic Neuroscience · doi:10.1016/j.autneu.2009.04.004 · Cited by 54
Bencsik, A., Muselli, L., Leboidre, M., Lakhdar, L., & Baron, T. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000137 · Cited by 48
Gut microbiota as a potential player in mn-induced neurotoxicity
Tinkov, A. A., Martins, A. C., Avila, D. S., Gritsenko, V. A., Skalny, A. V., Santamaria, A., Lee, E., Bowman, A. B., & Aschner, M. (2021) · Biomolecules · doi:10.3390/biom11091292 · Cited by 45
Wang, Q., Liu, J., Guo, Y., Dong, G., Zou, W., & Chen, Z. (2019) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20198443 · Cited by 45
Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates
Resnikoff, H., Metzger, J. M., Lopez, M., Bondarenko, V., Mejia, A., Simmons, H. A., & Emborg, M. E. (2019) · Journal of Inflammation Research · doi:10.2147/jir.s196552 · Cited by 42
Seguella, L., Sarnelli, G., & Esposito, G. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.270308 · Cited by 35
Deep Nasal Sinus Cavity Microbiota Dysbiosis in Parkinson’s Disease
Pal, G., Ramirez, V., Engen, P. A., Naqib, A., Forsyth, C. B., Green, S. J., Mahdavinia, M., Batra, P. S., Tajudeen, B. A., & Keshavarzian, A. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00254-y · Cited by 28
Drobny, A., Ngo, P. A., Neurath, M. F., Zunke, F., & López-Posadas, R. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655123 · Cited by 24
Jia, X., Chen, Q., Zhang, Y., & Asakawa, T. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1296713 · Cited by 22
Epprecht, L., Schreglmann, S. R., Goetze, O., Woitalla, D., Baumann, C. R., & Waldvogel, D. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7799-z · Cited by 12
Kim, E.-J., Vatsavayai, S., & Seeley, W. W. (2016) · The Behavioral Neurology of Dementia · doi:10.1017/9781139924771.008 · Cited by 7
Metadata
- Authors
- Braak, H., de Vos, R. A. I., Bohl, J., & Del Tredici, K.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Braak, Heiko
- ORCID
- Braak, Heiko
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 396
- Issue
- 1
- Pages
- 67-72
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2142483035
- Semantic Scholar
- 7f376c4b1f3f257ebbc010f8a10aba2ddeebcdcd
- Cited by
- 1,354
- References
- 33
- Citations by year
- 2026: 61 · 2025: 76 · 2024: 82 · 2023: 83 · 2022: 111 · 2021: 128 · 2020: 92 · 2019: 85 · 2018: 72 · 2017: 81 · 2016: 70 · 2015: 55 · 2014: 59 · 2013: 48 · 2012: 61
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, alpha-synuclein, synucleinopathies, submucosal plexus, myenteric plexus, submucosal neurons, enteric nervous system, brainstem, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Axonal Transport, Brain, Inclusion Bodies, Female, Gastric Mucosa, Humans, Male, Middle Aged, Models, Neurological, Myenteric Plexus, Nerve Net, Neural Pathways, Neurons, Parkinson Disease, Prions, Submucous Plexus, Vagus Nerve, Protein Folding, Disease Transmission, Infectious, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
